DLX2: Distal-Less Homeobox 2 - A Key Regulator of Craniofacial and Neuronal Development
Comprehensive genomic and functional analysis of DLX2, a homeobox transcription factor implicated in craniofacial development, neurogenesis, and cancer.
Gene Information Card
| Symbol | DLX2 |
|---|---|
| Full Name | Distal-Less Homeobox 2 |
| Gene Type | Protein-coding |
| Chromosomal Location | 2q31.1 |
| NCBI Gene ID | 1748 ncbi.nlm.nih.gov/gene/1748 |
| Ensembl ID | ENSG00000125844 |
| UniProt ID | Q07687 |
| OMIM ID | 126255 |
| HGNC ID | 2916 |
| Aliases | TES1, TES-1, DLX2A, DLX2B, Homeobox protein DLX-2 |
Description
DLX2 (Distal-Less Homeobox 2) is a protein-coding gene that encodes a member of the DLX homeobox transcription factor family. It plays a critical role in embryonic development, particularly in craniofacial morphogenesis, limb development, and neuronal differentiation. DLX2 functions as a transcriptional activator or repressor by binding to specific DNA sequences via its homeodomain. It is involved in the development of the forebrain, branchial arches, and sensory organs. Dysregulation of DLX2 has been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Craniofacial abnormalities (e.g., cleft palate) | DLX2 mutations disrupt homeobox-mediated transcriptional regulation during branchial arch development, leading to impaired palatogenesis and mandibular development. | OMIM #126255; PMID: 10861285 |
| Schizophrenia | Altered DLX2 expression in the prefrontal cortex may affect GABAergic interneuron migration and differentiation, contributing to neurodevelopmental deficits. | PMID: 16936727; ClinVar |
| Breast cancer | DLX2 overexpression promotes epithelial-mesenchymal transition (EMT) and metastasis via transcriptional activation of SNAI1 and TWIST1. | COSMIC; PMID: 25609832 |
| Colorectal cancer | DLX2 upregulation correlates with poor prognosis and enhances cell proliferation and invasion through Wnt/β-catenin signaling. | COSMIC; PMID: 29367642 |
| Glioblastoma | DLX2 is highly expressed in glioma stem cells and maintains stemness by regulating NOTCH and Hedgehog pathways. | COSMIC; PMID: 23563181 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Brain (cerebellum) | 8.3 | Low |
| Salivary gland | 6.7 | Low |
| Testis | 5.2 | Low |
| Thyroid | 4.1 | Low |
| Lung | 3.8 | Low |
| Kidney | 2.9 | Not detected |
| Liver | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression; used in neuronal differentiation studies |
| MCF7 (breast cancer) | 9.8 | Moderate expression; associated with EMT |
| HCT116 (colorectal cancer) | 11.4 | High expression; linked to proliferation |
| U87MG (glioblastoma) | 18.7 | Very high expression; stem cell marker |
| HEK293 (embryonic kidney) | 2.1 | Low expression; baseline control |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.500G>A (p.Arg167Gln) | Missense | <0.01% | Alters DNA-binding affinity; associated with craniofacial defects (ClinVar) |
| c.742C>T (p.Arg248*) | Nonsense | <0.01% | Premature truncation; loss of function (ClinVar) |
| c.103_104insC (p.Leu35Profs*12) | Frameshift | <0.01% | Loss of homeodomain; likely pathogenic (ClinVar) |
| c.421A>G (p.Ile141Val) | Missense | 0.02% | Rare variant; uncertain significance (ClinVar) |
| c.1A>G (p.Met1?) | Start loss | <0.01% | Loss of translation initiation; likely pathogenic (ClinVar) |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg248*, p.Leu35Profs*12) lead to truncated proteins lacking the homeodomain, abolishing DNA binding and transcriptional activity. These are associated with craniofacial developmental disorders.
Gain of Function (GOF)
Missense mutations (e.g., p.Arg167Gln) may alter DNA-binding specificity or enhance transcriptional activation, potentially contributing to oncogenic processes in breast and colorectal cancers.
Dominant Negative (DN)
No well-characterized dominant-negative mutations have been reported for DLX2. However, some missense variants in the homeodomain could theoretically interfere with wild-type protein function by competing for DNA binding.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (Reactome: R-HSA-201681)
• Notch signaling pathway (Reactome: R-HSA-157118)
• Hedgehog signaling pathway (Reactome: R-HSA-5358351)
• Epithelial-mesenchymal transition (EMT) (KEGG: hsa05205)
• Neural crest differentiation (PMID: 10861285)
Protein Summary
The DLX2 protein is a 328-amino acid homeobox transcription factor containing a conserved DNA-binding homeodomain. It localizes to the nucleus and regulates target gene expression by binding to TAAT/ATTA core motifs. DLX2 is essential for craniofacial and forebrain development, where it controls cell proliferation, migration, and differentiation. In cancer, DLX2 can act as an oncogene by promoting EMT, stemness, and metastasis. Post-translational modifications such as phosphorylation may modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DLX2 Knockout HEK293 Cell Line | EDJ-KQ4448 | Human | 1746 | Details Get a Quote |
| DLX2 Knockout HCT 116 Cell Line | EDJ-KQ26999 | Human | 1746 | Details Get a Quote |
| DLX2 Knockout HeLa Cell Line | EDJ-KQ27000 | Human | 1746 | Details Get a Quote |
| DLX2 Knockout A-549 Cell Line | EDJ-KQ61561 | Human | 1746 | Details Get a Quote |
